Bioprosthetic valves have been used to replace pathologic cardiac valves in humans for almost 20 years. Bioprostheses fail in adults after 7-10 years from tissue degeneration and calcification. In young patients they fail sooner, and are contraindicated. How can the bioprostheses be made to last longer? The proposed research addresses this question. Bioprostheses are made in a variety of designs, such as flexible or nonflexible stents, cylindrical or spherical leaflets, prepared in the closed or open position, and fixed at higher or lower pressures. They are made from various materials such as porcine aortic valves, bovine pericardium, human dura mater, or human fascia lata. Since all bioprostheses are meant to perform the function of natural cardiac valves, their short functional life may be the result of their failure to duplicate the design of natural cardiac valves. Our goal is to establish a scientific approach to the design of an ideal aortic bioprosthesis. Standard porcine and pericardial bioprostheses will be implanted in the aortic position in calves and investigated for their design parameters and stress-strain properties. The performance of the bioprostheses will be determined in terms of the changes in leaflet dynamics, stress-strain properties, and tissue structure as a function of duration of implantation. Their longevity will be determined in terms of leaflet degeneration and calcification. The ways in which their design and properties differ from those of the natural aortic valve will be established. Their design will be correlated with their performance in order to understand how leaflet geometry affects leaflet dynamics, how stress-strain properties affect stresses in vivo, and how these stresses cause leaflet degeneration or calcification. Based upon this understanding and upon our knowledge of the natural valve, we will establish the design of an ideal bioprosthesis. New porcine and pericardial bioprostheses will be prepared in which the design and the properties will be those of the ideal. The new bioprostheses will be investigated to demonstrate that their performance and longevity are better than those of standard bioprostheses. The success of this research will benefit many patients requiring valve replacement.